Klebsiella pneumoniae that produce carbapenemases such as the K. pneumoniae carbapenemase (blaKPC) are an increasingly common multidrug resistant pathogen causing nosocomial infections and outbreaks, with high rates of morbidity and mortality worldwide. Horizontal transfer of carbapenemase-producing plasmids is believed to play a significant role in the spread of multidrug resistant K. pneumoniae and other Gram-negative bacteria. Our experiments are aimed at defining the parameters regulating the spread of carbapenem resistance. Patients can be colonized by KPC+ K. pneumoniae for extended periods of time; however, only some of these patients have evidence of blaKPC containing plasmids transferring to bacteria other than Klebsiella species based on our extensive surveillance system. Understanding any differences between in vitro potential to spread and in vivo evidence of spread will aid our attempts to prevent dissemination of the resistance phenotype.